Neoadjuvant Docetaxel Plus Cisplatin and 5-fluorouracil (TPF) Followed by Radiotherapy Plus Concomitant Chemo or Cetuximab Versus Radiotherapy Plus Concomitant Chemo or Cetuximab in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck. A Randomized Phase III Factorial Study.
This multicenter open label randomised phase III study is the implementation of a previous
phase II randomized trial evaluating the efficacy of chemoradiotherapy with or without
neoadjuvant TPF chemotherapy in locally advanced Head and Neck cancer. Assuming a
randomisation ratio of 1:1, using the Mantel-Cox version of the log-rank test, 204 events
are required in order to achieve a power of 0.80 of detecting an hazard ratio of 0.675 in
favour of the experimental treatment with a type I error of 0.05, two-sided. With a uniform
accrual of 4 years and a follow-up of 2 further years, the total number of required patients
is 420 (210 per arm) to detect an absolute difference of 12% in 3 year overall survival in
favour of the neoadjuvant arm (from 52.5% to 64.5%).Since the 101 patients randomized in the
phase II part of the study will be included in the final analysis, 319 new patients are
needed to complete the trial.The total number of 420 patients will be able to detect a
difference of 10%, (from 35% to 45%) in terms of grade 3/4 in-field mucosal toxicity during
the concomitant treatment (radiotherapy plus chemo or cetuximab) with a power of 80%. Within
the H&N07 trials was introduced a sub-study that allows to investigate the value of
circulating marker evaluation as predictor of response to anti EGFR therapy in patients with
cancer of the head and neck.
The expression level analysis of circulating biological markers will be evaluated on blood
collected during therapy. The analysis will concern the following biological
markers:Cytokines angiogenesis and cell adhesion molecules; Proteins involved in the EGFR
signaling pathway (EGF, TGF-a, s-EGFR);circulating tumor cells (CTC) and circulating
endothelial cells (CEC).
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
overall survival defined as the time from the date of randomization to the date of death from any cause.
Italy: The Italian Medicines Agency